Resolution of apolipoprotein A1 and A2 proteoforms: their cardiometabolic correlates and implications for future research
Purpose of review
A ‘proteoform’ is defined as one specific protein structural form that results from the combination of allelic variation, alternative RNA splicing, and/or posttranslational modifications (PTMs) in specific locations on the amino acid backbone. Apolipoproteins A1 and A2 are highly abundant apolipoproteins that mediate HDL structure and function. ApoA1 and apoA2 are known to undergo PTMs, which results in multiple proteoforms. However, the catalogue of apoA1 and apoA2 proteoforms as well as their associations with cardiometabolic health characteristics has not been described until recently. In this ...
Source: Current Opinion in Lipidology - August 1, 2022 Category: Lipidology Tags: HYPERLIPIDAEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
Lipoprotein (a) in familial hypercholesterolaemia
Purpose of review
The role of lipoprotein (a) in atherogenesis has been the subject of argument for many years. Evidence that it is raised in familial hypercholesterolaemia has been disputed not least because a mechanism related to low density lipoprotein (LDL) receptor mediated catabolism has been lacking. Whether lipoprotein (a) increases the already raised atherosclerotic cardiovascular disease (ASCVD) risk in familial hypercholesterolaemia is also more dubious than is often stated. We review the evidence in an attempt to provide greater clarity.
Recent findings
Lipoprotein (a) levels are raised as a conseque...
Source: Current Opinion in Lipidology - August 1, 2022 Category: Lipidology Tags: HYPERLIPIDAEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
How should low-density lipoprotein cholesterol be calculated in 2022?
Purpose of review
The reference method for low-density lipoprotein-cholesterol (LDL-C) quantitation is β-quantification, a technically demanding method that is not convenient for routine use. Indirect calculation methods to estimate LDL-C, including the Friedewald equation, have been used since 1972. This calculation has several recognized limitations, especially inaccurate results for triglycerides (TG)>4.5 mmol/l (>400 mg/dl). In view of this, several other equations were developed across the world in different datasets.
The purpose of this review was to analyze the best method to calculate LDL-C in clinical ...
Source: Current Opinion in Lipidology - August 1, 2022 Category: Lipidology Tags: HYPERLIPIDAEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
Cascade screening for familial hypercholesterolemia should be organized at a national level
Purpose of review
Patients with familial hypercholesterolemia (FH) have a markedly increased risk of premature cardiovascular disease. However, there are effective lipid-lowering therapies available to reduce the risk of cardiovascular disease. This makes it important to diagnose these patients. The most cost-effective strategy to diagnose patients with FH is to perform cascade screening. However, cascade screening as part of ordinary healthcare has not been very successful. Thus, there is a need to implement more efficient cascade screening strategies.
Recent findings
Cascade screening for FH should be organize...
Source: Current Opinion in Lipidology - August 1, 2022 Category: Lipidology Tags: HYPERLIPIDAEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
Diagnosis of remnant hyperlipidaemia
Purpose of review
In recent years, there has been interest for the development of simplified diagnosis algorithms of dysbetalipoproteinemia (DBL) in order to avoid the complex testing associated with the Fredrickson criteria (reference method). The purpose of this review is to present recent advances in the field of DBL with a focus on screening and diagnosis.
Recent findings
Recently, two different multi-step algorithms for the diagnosis of DBL have been published and their performance has been compared to the Fredrickson criteria. Furthermore, a recent large study demonstrated that only a minority (38%) of DBL...
Source: Current Opinion in Lipidology - August 1, 2022 Category: Lipidology Tags: HYPERLIPIDAEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
What should be the goal of cholesterol-lowering treatment? A quantitative evaluation dispelling guideline myths
Purpose of review
Guidelines for cholesterol-lowering treatment generally include extensive review of epidemiological and clinical trial evidence. However, the next logical step, the translation of evidence into clinical advice, occurs not entirely by reasoning, but by a form of consensus in which the prejudices and established beliefs of the societies with interests in cardiovascular disease convened to interpret the evidence are prominent. Methods, which are the subject of this review, have, however, been developed by which clinical trial evidence can be translated objectively into best practice.
Recent findings
...
Source: Current Opinion in Lipidology - August 1, 2022 Category: Lipidology Tags: HYPERLIPIDAEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. Durrington Source Type: research
Editorial introduction
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - August 1, 2022 Category: Lipidology Tags: EDITORIAL INTRODUCTION Source Type: research
Considerations for routinely testing for high Lp(a)
Purpose of review
Lipoprotein(a) (Lp[a]) is a likely causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve disease, confirmed by Mendelian randomization. With reliable assays, it has been established that Lp(a) is linearly associated with ASCVD. Current low-density lipoprotein cholesterol (LDL-C) lowering therapies do not or minimally lower Lp(a). This review focuses on the clinical importance and therapeutic consequences of Lp(a) measurement.
Recent findings
Development of RNA-based Lp(a) lowering therapeutics has positioned Lp(a) as one of the principal residual risk factors to...
Source: Current Opinion in Lipidology - June 1, 2022 Category: Lipidology Tags: EDITORIAL COMMENTS Source Type: research
Nutrition and its impact on cardiovascular disease
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - June 1, 2022 Category: Lipidology Tags: EDITORIAL COMMENTS Source Type: research
Atherosclerosis: cell biology and lipoproteins
No abstract available (Source: Current Opinion in Lipidology)
Source: Current Opinion in Lipidology - June 1, 2022 Category: Lipidology Tags: EDITORIAL COMMENTS Source Type: research
Sphingosine-1-phosphate: metabolism, transport, atheroprotection and effect of statin treatment
Purpose of review
To better define the metabolism of sphingosine-1-phosphate (S1P), its transport in plasma and its interactions with S1P receptors on vascular cells, and to evaluate the effect of statin treatment on the subnormal plasma levels of high-density lipoprotein (HDL)-bound S1P characteristic of the atherogenic dyslipidemia of metabolic syndrome (MetS).
Recent findings
Neither clinical intervention trials targeted to raising high-density lipoprotein-cholesterol (HDL-C) levels nor human genome-wide association studies (GWAS) studies have provided evidence to support an atheroprotective role of HDL. Rece...
Source: Current Opinion in Lipidology - June 1, 2022 Category: Lipidology Tags: LIPID METABOLISM: Edited by John Chapman Source Type: research
The expanding role of lyso-phosphatidylcholine acyltransferase-3 (LPCAT3), a phospholipid remodeling enzyme, in health and disease
Purpose of review
The turnover of fatty acids (FAs) at the sn-2 position of phospholipids is mediated by the reciprocal actions of phospholipases A2 and lyso-PL acyltransferases (LPLAT). LPCAT3, a major LPLAT isoform, exhibits a strong specificity for polyunsaturated FAs s (PUFAs). Although the enzyme was originally studied in the context of cardiometabolism, recent investigations have shed light on the role of LPCAT3 in other tissues such as skeletal muscle and in unexpected biological processes such as cell death and oncogenesis.
Recent findings
The three-dimensional structure of LPCAT3 has been elucidated all...
Source: Current Opinion in Lipidology - June 1, 2022 Category: Lipidology Tags: LIPID METABOLISM: Edited by John Chapman Source Type: research
Understanding the ins and outs of lipoprotein (a) metabolism
Purpose of review
This review summarizes our current understanding of the processes of apolipoprotein(a) secretion, assembly of the Lp(a) particle and removal of Lp(a) from the circulation. We also identify existing knowledge gaps that need to be addressed in future studies.
Recent findings
The Lp(a) particle is assembled in two steps: a noncovalent, lysine-dependent interaction of apo(a) with apoB-100 inside hepatocytes, followed by extracellular covalent association between these two molecules to form circulating apo(a).
The production rate of Lp(a) is primarily responsible for the observed inverse correlat...
Source: Current Opinion in Lipidology - June 1, 2022 Category: Lipidology Tags: LIPID METABOLISM: Edited by John Chapman Source Type: research
Lymphatics - not just a chylomicron conduit
Purpose of review
Lymphatics are known to have active, regulated pumping by smooth muscle cells that enhance lymph flow, but whether active regulation of lymphatic pumping contributes significantly to the rate of appearance of chylomicrons (CMs) in the blood circulation (i.e., CM production rate) is not currently known. In this review, we highlight some of the potential mechanisms by which lymphatics may regulate CM production.
Recent findings
Recent data from our lab and others are beginning to provide clues that suggest a more active role of lymphatics in regulating CM appearance in the circulation through var...
Source: Current Opinion in Lipidology - June 1, 2022 Category: Lipidology Tags: LIPID METABOLISM: Edited by John Chapman Source Type: research
Macrophage SR-B1 in atherosclerotic cardiovascular disease
Purpose of review
Scavenger receptor class B type 1 (SR-B1) promotes atheroprotection through its role in HDL metabolism and reverse cholesterol transport in the liver. However, evidence indicates that SR-B1 may impact atherosclerosis through nonhepatic mechanisms.
Recent findings
Recent studies have brought to light various mechanisms by which SR-B1 affects lesional macrophage function and protects against atherosclerosis. Efferocytosis is efficient in early atherosclerotic lesions. At this stage, and beyond its role in cholesterol efflux, SR-B1 promotes free cholesterol-induced apoptosis of macrophages through...
Source: Current Opinion in Lipidology - June 1, 2022 Category: Lipidology Tags: LIPID METABOLISM: Edited by John Chapman Source Type: research
